О некоторых вопросах перевода произведений И.Э. Бабеля на венгерский язык

The author of the study first examines those common features of Isaac Babel's literary works which determine the possibility of translation; later he mentions some characteristic notions of Hungarian translators, Hungarian publications and the premises for the reaction to them. In connection with the translation of concrete works the author points out cases of mistranslation, which are luckily not too many, then analyses the cases in detail in which the translator's task is more or less difficult. He indicates typical cases where adequate and precise translation becomes impossible: he refers to phraseologism and cases of word-by-word Russian translation from Yiddish

The Divinity of Crime: How spirituality can strengthen the resilience of criminal organizations

This thesis conducts a systematic analysis of open source data that discusses ideational factors of resilience in criminal organizations. It does this by looking at the role of spirituality – referred to as an individual’s moral or ethical codes influenced by cultural, ethnic, and religious values – and its effects on an organization’s durability, impenetrability, and adaptability. To understand spirituality as a factor of resilience in criminal organizations, it is delineated into four Dimensions of Spiritual Influence (DoSI). They are (1) trust, (2) spiritual neutralization, (3) strategic arenas, and (4) the logistical use of spiritual institutions. In order to analyze the role of spirituality as an element of resilience within criminal organizations, this thesis employs a systematic analysis of open source data and literature in order to collect, review, and analyze the existing secondary literature. These themes are applied to four criminal organizations in order to create a better understanding of the extent of spirituality’s influence on these organizations. The criminal organizations analyzed are (1) Jewish organized crime, (2) the Cosa Nostra, (3) the Vory v Zakone, and (4) La Familia Michoacana/Knights Templar. This analysis highlights the potential influence spirituality can have on an organization’s resilience against disruption by law enforcement and rival criminal organizations

How Can Viral Dynamics Models Inform Endpoint Measures in Clinical Trials of Therapies for Acute Viral Infections?

Acute viral infections pose many practical challenges for the accurate assessment of the impact of novel therapies on viral growth and decay. Using the example of influenza A, we illustrate how the measurement of infection-related quantities that determine the dynamics of viral load within the human host, can inform investigators on the course and severity of infection and the efficacy of a novel treatment. We estimated the values of key infection-related quantities that determine the course of natural infection from viral load data, using Markov Chain Monte Carlo methods. The data were placebo group viral load measurements collected during volunteer challenge studies, conducted by Roche, as part of the oseltamivir trials. We calculated the values of the quantities for each patient and the correlations between the quantities, symptom severity and body temperature. The greatest variation among individuals occurred in the viral load peak and area under the viral load curve. Total symptom severity correlated positively with the basic reproductive number. The most sensitive endpoint for therapeutic trials with the goal to cure patients is the duration of infection. We suggest laboratory experiments to obtain more precise estimates of virological quantities that can supplement clinical endpoint measurements

Consistent avoidance of human disturbance over large geographical distances by a migratory bird

Recent work on animal personalities has demonstrated that individuals may show consistent behaviour across situations and contexts. These studies were often carried out in one location and/or during short time intervals. Many animals, however, migrate and spend their life in several geographically distinct locations, and they may either adopt behaviours specific to the local environment or keep consistent behaviours over ecologically distinct locations. Long-distance migratory species offer excellent opportunities to test whether the animals maintain their personalities over large geographical scale, although the practical difficulties associated with these studies have hampered such tests. Here, we demonstrate for the first time consistency in disturbance tolerance behaviour in a long-distance migratory bird, using the common crane Grus grus as an ecological model species. Cranes that hatched in undisturbed habitats in Finland choose undisturbed migratory stop-over sites in Hungary, 1300–2000 km away from their breeding ground. This is remarkable, because these sites are not only separated by large distances, they also differ ecologically: the breeding sites are wooded bogs and subarctic tundra, whereas the migratory stop-over sites are temperate zone alkaline grasslands. The significance of our study goes beyond evolutionary biology and behavioural ecology: local effects on behaviour may carry over large distances, and this hitherto hidden implication of habitat selection needs to be incorporated into conservation planning

ОСОБЕННОСТИ ОРГАНИЗАЦИОННОЙ КУЛЬТУРЫ МАЛЫХ И СРЕДНИХ ПРЕДПРИНИМАТЕЛЬСТВ (на основе результатов анкетирования работников венгерских и российских фирм)

In article the author on the basis of questioning employees of Hungarianand Russian firms exmined aspects ofthe organizational culture of small andmedium-sized companies, such as: therelationship between employees andtheir communication, communication and communication between employees andmanagers, staff’s knowledge in matters of the company, career opportunities,employment opportunities of higher positions in the firm.В статьи на основе анкетирования сотрудников венгерских и российских фирм расcматриваются такие аспекты организационной культуры малых и средних фирм, как: связи между сотрудниками и их коммуникация; связи и коммуникация между работниками и руководителями; информированность работниковввопросахфирмы; возможности карьеры, возможности занятия более высоких должностей в фирме

Using Clinical Trial Simulators to Analyse the Sources of Variance in Clinical Trials of Novel Therapies for Acute Viral Infections.

BACKGROUND:About 90% of drugs fail in clinical development. The question is whether trials fail because of insufficient efficacy of the new treatment, or rather because of poor trial design that is unable to detect the true efficacy. The variance of the measured endpoints is a major, largely underestimated source of uncertainty in clinical trial design, particularly in acute viral infections. We use a clinical trial simulator to demonstrate how a thorough consideration of the variability inherent in clinical trials of novel therapies for acute viral infections can improve trial design. METHODS AND FINDINGS:We developed a clinical trial simulator to analyse the impact of three different types of variation on the outcome of a challenge study of influenza treatments for infected patients, including individual patient variability in the response to the drug, the variance of the measurement procedure, and the variance of the lower limit of quantification of endpoint measurements. In addition, we investigated the impact of protocol variation on clinical trial outcome. We found that the greatest source of variance was inter-individual variability in the natural course of infection. Running a larger phase II study can save up to $38 million, if an unlikely to succeed phase III trial is avoided. In addition, low-sensitivity viral load assays can lead to falsely negative trial outcomes. CONCLUSIONS:Due to high inter-individual variability in natural infection, the most important variable in clinical trial design for challenge studies of potential novel influenza treatments is the number of participants. 100 participants are preferable over 50. Using more sensitive viral load assays increases the probability of a positive trial outcome, but may in some circumstances lead to false positive outcomes. Clinical trial simulations are powerful tools to identify the most important sources of variance in clinical trials and thereby help improve trial design

Health economic analyses of latent tuberculosis infection screening and preventive treatment among people living with HIV in lower tuberculosis incidence settings: a systematic review [version 1; peer review: awaiting peer review]

INTRODUCTION: In lower tuberculosis (TB) incidence countries (<100 cases/100,000/year), screening and preventive treatment (PT) for latent TB infection (LTBI) among people living with HIV (PLWH) is often recommended, yet guidelines advising which groups to prioritise for screening can be contradictory and implementation patchy. Evidence of LTBI screening cost-effectiveness may improve uptake and health outcomes at reasonable cost. METHODS: Our systematic review assessed cost-effectiveness estimates of LTBI screening/PT strategies among PLWH in lower TB incidence countries to identify model-driving inputs and methodological differences. Databases were searched 1980-2020. Studies including health economic evaluation of LTBI screening of PLWH in lower TB incidence countries (<100 cases/100,000/year) were included. Study quality was assessed using the CHEERS checklist. RESULTS: Of 2,644 articles screened, nine studies were included. Cost-effectiveness estimates of LTBI screening/PT for PLWH varied widely, with universal screening/PT found highly cost-effective by some studies, while only targeting to high-risk groups (such as those from mid/high TB incidence countries) deemed cost-effective by others. Cost-effectiveness of strategies screening all PLWH from studies published in the past five years varied from US$2828 to US$144,929/quality-adjusted life-year gained (2018 prices). Study quality varied, with inconsistent reporting of methods and results limiting comparability of studies. Cost-effectiveness varied markedly by screening guideline, with British HIV Association guidelines more cost-effective than NICE guidelines in the UK. DISCUSSION: Cost-effectiveness studies of LTBI screening/PT for PLWH in lower TB incidence settings are scarce, with large variations in methods and assumptions used, target populations and screening/PT strategies evaluated. The limited evidence suggests LTBI screening/PT may be cost-effective for some PLWH groups but further research is required, particularly on strategies targeting screening/PT to PLWH at higher risk. Standardisation of model descriptions and results reporting could facilitate reliable comparisons between studies, particularly to identify those factors driving the wide disparity between cost-effectiveness estimates. REGISTRATION: PROSPERO CRD42020166338 (18/03/2020)

Health economic analyses of latent tuberculosis infection screening and preventive treatment among people living with HIV in lower tuberculosis incidence settings: a systematic review [version 2; peer review: 1 approved, 1 approved with reservations]

INTRODUCTION: In lower tuberculosis (TB) incidence countries (<100 cases/100,000/year), screening and preventive treatment (PT) for latent TB infection (LTBI) among people living with HIV (PLWH) is often recommended, yet guidelines advising which groups to prioritise for screening can be contradictory and implementation patchy. Evidence of LTBI screening cost-effectiveness may improve uptake and health outcomes at reasonable cost. METHODS: Our systematic review assessed cost-effectiveness estimates of LTBI screening/PT strategies among PLWH in lower TB incidence countries to identify model-driving inputs and methodological differences. Databases were searched 1980-2020. Studies including health economic evaluation of LTBI screening of PLWH in lower TB incidence countries (<100 cases/100,000/year) were included. RESULTS: Of 2,644 articles screened, nine studies were included. Cost-effectiveness estimates of LTBI screening/PT for PLWH varied widely, with universal screening/PT found highly cost-effective by some studies, while only targeting to high-risk groups (such as those from mid/high TB incidence countries) deemed cost-effective by others. Cost-effectiveness of strategies screening all PLWH from studies published in the past five years varied from US$2828 to US$144,929/quality-adjusted life-year gained (2018 prices). Study quality varied, with inconsistent reporting of methods and results limiting comparability of studies. Cost-effectiveness varied markedly by screening guideline, with British HIV Association guidelines more cost-effective than NICE guidelines in the UK. DISCUSSION: Cost-effectiveness studies of LTBI screening/PT for PLWH in lower TB incidence settings are scarce, with large variations in methods and assumptions used, target populations and screening/PT strategies evaluated. The limited evidence suggests LTBI screening/PT may be cost-effective for some PLWH groups but further research is required, particularly on strategies targeting screening/PT to PLWH at higher risk. Standardisation of model descriptions and results reporting could facilitate reliable comparisons between studies, particularly to identify those factors driving the wide disparity between cost-effectiveness estimates. REGISTRATION: PROSPERO CRD42020166338 (18/03/2020)

Plasma proteomic profiling in postural orthostatic tachycardia syndrome (POTS) reveals new disease pathways

Postural orthostatic tachycardia syndrome (POTS) is a cardiovascular autonomic disorder characterized by excessive heart rate increase on standing, leading to debilitating symptoms with limited therapeutic possibilities. Proteomics is a large-scale study of proteins that enables a systematic unbiased view on disease and health, allowing stratification of patients based on their protein background. The aim of the present study was to determine plasma protein biomarkers of POTS and to reveal proteomic pathways differentially regulated in POTS. We performed an age- and sex-matched, case–control study in 130 individuals (case–control ratio 1:1) including POTS and healthy controls. Mean age in POTS was 30 ± 9.8 years (84.6% women) versus controls 31 ± 9.8 years (80.0% women). We analyzed plasma proteins using data-independent acquisition (DIA) mass spectrometry. Pathway analysis of significantly differently expressed proteins was executed using a cutoff log2 fold change set to 1.2 and false discovery rate (p-value) of < 0.05. A total of 393 differential plasma proteins were identified. Label-free quantification of DIA-data identified 30 differentially expressed proteins in POTS compared with healthy controls. Pathway analysis identified the strongest network interactions particularly for proteins involved in thrombogenicity and enhanced platelet activity, but also inflammation, cardiac contractility and hypertrophy, and increased adrenergic activity. Our observations generated by the first use a label-free unbiased quantification reveal the proteomic footprint of POTS in terms of a hypercoagulable state, proinflammatory state, enhanced cardiac contractility and hypertrophy, skeletal muscle expression, and adrenergic activity. These findings support the hypothesis that POTS may be an autoimmune, inflammatory and hyperadrenergic disorder

Limited Tumor Tissue Drug Penetration Contributes to Primary Resistance against Angiogenesis Inhibitors

Resistance mechanisms against antiangiogenic drugs are unclear. Here, we correlated the antitumor and antivascular properties of five different antiangiogenic receptor tyrosine kinase inhibitors (RTKIs) (motesanib, pazopanib, sorafenib, sunitinib, vatalanib) with their intratumoral distribution data obtained by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). In the first mouse model, only sunitinib exhibited broad-spectrum antivascular and antitumor activities by simultaneously suppressing vascular endothelial growth factor receptor-2 (VEGFR2) and desmin expression, and by increasing intratumoral hypoxia and inhibiting both tumor growth and vascularisation significantly. Importantly, the highest and most homogeneous intratumoral drug concentrations have been found in sunitinib-treated animals. In another animal model, where - in contrast to the first model - vatalanib was detectable at homogeneously high intratumoral concentrations, the drug significantly reduced tumor growth and angiogenesis. In conclusion, the tumor tissue penetration and thus the antiangiogenic and antitumor potential of antiangiogenic RTKIs vary among the tumor models and our study demonstrates the potential of MALDI-MSI to predict the efficacy of unlabelled small molecule antiangiogenic drugs in malignant tissue. Our approach is thus a major technical and preclinical advance demonstrating that primary resistance to angiogenesis inhibitors involves limited tumor tissue drug penetration. We also conclude that MALDI-MSI may significantly contribute to the improvement of antivascular cancer therapies